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10.1245/s10434-006-9320-5
Annals of Surgical Oncology 14:1565-1574 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Change of E-Cadherin by Hepatocyte Growth Factor and Effects on the Prognosis of Hypopharyngeal Carcinoma

Chul-Ho Kim, MD, PhD1,2, JangHee Kim, MD3, Hison Kahng, MD1,2 and Eun Chang Choi, MD, PhD4

1 Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea
2 Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Korea
3 Department of Pathology, School of Medicine, Ajou University, Suwon, Korea
4 Department of Otorhinolaryngology, College of Medicine, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul, 120-752, Korea

Correspondence: Address correspondence and reprint requests to: Eun Chang Choi, MD, PhD; E-mail: ostium{at}ajou.ac.kr

Background: Hepatocyte growth factor (HGF) is known to induce scattering in various epithelial cells, and E-cadherin plays important roles in the maintenance of cell-cell adhesion. However, the mechanisms surrounding these actions are not fully understood. Therefore, we examined how HGF affects the expression and distribution of E-cadherin. In addition, we observed the relationship between prognosis and modulation of E-cadherin by HGF in hypopharyngeal carcinoma.

Methods: Tumor tissues from 66 patients with hypopharyngeal squamous cell carcinoma were evaluated for the expression of HGF, its receptor (c-Met), and E-cadherin. Reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot test were performed on hypopharyngeal cancer tissues. The association and changes of E-cadherin with HGF treatment in a hypopharyngeal cancer cell line were investigated by RT-PCR, Western blot analysis, inhibition assay, immunofluorescence staining, and invasion assay.

Results: E-cadherin expression was found in 87.9% of squamous cell carcinomas; these could be further classified as membranous type (46.9%) or nonmembranous type (53.1%). The expression of HGF in tumors with nonmembranous type E-cadherin expression was far higher than in tumors with membranous expression. Nonmembranous type E-cadherin expression correlated significantly with lymph node metastasis, distant metastasis, and recurrence (P < .05). HGF decreased the expression of E-cadherin and induced the translocation of E-cadherin to the cytoplasm. HGF and E-cadherin neutralizing antibody stimulated dispersion, and HGF significantly enhanced the invasion of hypopharyngeal cancer cells in a dose-dependent manner (P < .05).

Conclusions: These results suggest that HGF can modulate the expression and intracellular localization of E-cadherin in hypopharyngeal cancer cells. In addition, these results indicate that changes in E-cadherin by HGF can affect the prognosis of hypopharyngeal carcinoma.

Key Words: HGF • E-cadherin • Hypopharyngeal cancer






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